Combined hepatocellular cholangiocarcinoma (cHCC-CC): an update of genetics, molecular biology, and therapeutic interventions

Abstract

Combined hepatocellular cholangiocarcinoma (CC) is a rare and aggressive primary hepatic malignancy with significant histological and biological heterogeneity. It presents with more aggressive behavior and worse survival outcomes than either hepatocellular carcinoma or CC and remains a diagnostic challenge. An accurate diagnosis is crucial for its optimal management. Major hepatectomy with hilar node resection remains the mainstay of treatment in operable cases. Advances in the genetic and molecular characterization of this tumor will contribute to the better understanding of its pathogenesis and shape its future management.

Keywords: cholangiocarcinoma; combined; genetics; hepatocellular carcinoma; mixed liver tumors; molecular biology; primary liver cancer; treatment.

Figure 1

(A) Combined hepatocellular and cholangiocellular carcinoma. A single tumor nodule shows two different histological components, one with glandular differentiation and biliary immunoprofile consistent with cholangiocarcinoma (upper area of the picture) and one with a well-to-moderately differentiated hepatocellular carcinoma (lower part of the picture); H&E staining. (B) Moderately differentiated HCC, trabecular pattern. Cellular variability with scattered large hyperchromatic nuclei; H&E staining, 100×. (C) Moderately differentiated intrahepatic cholangiocarcinoma. Glandular structures are variable in size and shape, in a sclerosed stroma; H&E staining, 100×.